Thursday, May 25, 2017

Lit Bits: May 25, 2017

From the recent literature...

1. Recent PE Research

A. PE and DVT in Pts Hospitalized With Syncope: A Multicenter Cross-sectional Study in Toronto, Ontario, Canada

Verma AA, et al. JAMA Intern Med. Published online May 8, 2017.

This study is a response to Prandoni et al. NEJM 2017 here:

The prevalence of pulmonary embolism (PE) among patients hospitalized with syncope is uncertain. The recently published Pulmonary Embolism in Syncope Italian Trial (PESIT)1 systematically evaluated patients hospitalized with a first episode of syncope and determined that 17.3% had a PE. It is not known how commonly patients hospitalized with syncope are investigated for PE or deep venous thrombosis (DVT) in routine practice.

Methods | We conducted a retrospective cross-sectional study at 4 hospital sites in Toronto, Ontario, Canada, that were participating in the General Medicine Inpatient (GEMINI) cohort study. The GEMINI study has linked electronic clinical data from hospital information systems with administrative data to study patients cared for by general medicine services in hospitals affiliated with the University of Toronto. We applied the same inclusion and exclusion criteria as PESIT in all general medicine patients hospitalized through the emergency department between April 1, 2011, and March 31, 2015. In Canada, hospitals use International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10), codes to designate 1 primary diagnosis for the emergency department visit and 1 primary diagnosis at hospital discharge for mandatory reporting to the Canadian Institute for Health Information. The emergency department and hospital discharge diagnoses are not necessarily the same. We included patients if their primary diagnosis was syncope in either the emergency department or at hospital discharge, using the ICD-10 code R55. We excluded patients who were receiving anticoagulation at admission, had prior syncope, or were pregnant.

The main outcomes were the occurrence of investigation for venous thromboembolism (VTE) during hospitalization, defined as testing with a plasma D-dimer level, compression ultrasonography of the upper or lower limbs, computed tomographic pulmonary angiography (
CTPA), or ventilation perfusion (V/Q) scan, and the diagnostic yield of these investigations. Because there is substantial overlap in the investigation and management of DVT and PE, we examined a composite of all investigations for VTE. The GEMINI study received research ethics board approval from all participating hospitals.

Results | Of the 1650 patients hospitalized with syncope, 345 were excluded (179 with preadmission anticoagulation and 166 with previous syncope), and the final cohort included 1305 patients. At least 1 investigation for VTE was performed in 146 patients (11.2% [95%CI, 9.6%-13.0%]) (Table 1), including 120 who received imaging with CTPA, V/Q scan, and/or compression ultrasonography (9.2% [95% CI, 7.8%-10.9%]). Pulmonary embolism was diagnosed in 11 of the 73 patients who received a CTPA or V/Q scan, and DVT was diagnosed in 10 of the 67 patients who received ultrasonography, representing a diagnostic yield of 15.1% (95% CI, 8.6%-25.0%) and 14.9% (95% CI, 8.3%-25.4%), respectively. The prevalence of VTE in the cohort was 1.4% (95% CI, 0.9%-2.2%) (Table 2).

Discussion | In a large observational study, VTE was investigated in 11.2% of patients hospitalized with syncope. The diagnostic yield for VTE was 15.0% and the prevalence was 1.4%, not 41.9% and 17.1%, respectively, as found in the PESIT study.1 Our findings call into question the generalizability of the PESIT results.The1.4%prevalence of VTE we found is consistent with previously published estimates, which range from 0.9% to 2.8%.2-4 Unlike the case in PESIT, all patients were not screened for VTE in our study or in these previous studies; thus, the prevalence may have been underestimated. A more illuminating comparison, however, is to examine the diagnostic yield of imaging for VTE. We expected that thrombosis would be more likely in the selected patients who received imaging for VTE based on clinical judgment in our study, not in the large proportion (40.9%) of patients who received imaging based on screening, as was the case in PESIT. The reverse was true, highlighting the differences in the study populations…

Assessing all patients hospitalized with syncope for VTE would represent a substantial departure from conventional practice. Based on the available data, there is little, if any, justification for routine testing for VTE in all patients hospitalized with a first episode of syncope.

B. Low Yield of CTPA in the ED When Providers Override Evidence-based CDS.

Yan Z, et al. Radiology. 2017 Mar;282(3):717-725.

Purpose To determine the frequency of, and yield after, provider overrides of evidence-based clinical decision support (CDS) for ordering computed tomographic (CT) pulmonary angiography in the emergency department (ED).

Materials and Methods This HIPAA-compliant, institutional review board-approved study was performed at a tertiary care, academic medical center ED with approximately 60 000 annual visits and included all patients who were suspected of having pulmonary embolism (PE) and who underwent CT pulmonary angiography between January 1, 2011, and August 31, 2013. The requirement to obtain informed consent was waived. Each CT order for pulmonary angiography was exposed to CDS on the basis of the Wells criteria. For patients with a Wells score of 4 or less, CDS alerts suggested d-dimer testing because acute PE is highly unlikely in these patients if d-dimer levels are normal. The yield of CT pulmonary angiography (number of positive PE diagnoses/total number of CT pulmonary angiographic examinations) was compared in patients in whom providers overrode CDS alerts (by performing CT pulmonary angiography in patients with a Wells score ≤4 and a normal d-dimer level or no d-dimer testing) (override group) and those in whom providers followed Wells criteria (CT pulmonary angiography only in patients with Wells score over 4 or ≤4 with elevated d-dimer level) (adherent group). A validated natural language processing tool identified positive PE diagnoses, with subsegmental and/or indeterminate diagnoses removed by means of chart review. Statistical analysis was performed with the χ2 test, the Student t test, and logistic regression.

Results Among 2993 CT pulmonary angiography studies in 2655 patients, 563 examinations had a Wells score of 4 or less but did not undergo d-dimer testing and 26 had a Wells score of 4 or less and had normal d-dimer levels. The yield of CT pulmonary angiography was 4.2% in the override group (25 of 589 studies, none with a normal d-dimer level) and 11.2% in the adherent group (270 of 2404 studies) (P less than .001). After adjustment for the risk factor differences between the two groups, the odds of an acute PE finding were 51.3% lower when providers overrode alerts than when they followed CDS guidelines. Comparison of the two groups including only patients unlikely to have PE led to similar results.

Conclusion The odds of an acute PE finding in the ED when providers adhered to evidence presented in CDS were nearly double those seen when providers overrode CDS alerts. Most overrides were due to the lack of d-dimer testing in patients unlikely to have PE.

C. Low yield of ventilation and perfusion imaging for the evaluation of PE after indeterminate CT PA.

Curtis BR, et al. Emerg Radiol. 2017 Apr 12 [Epub ahead of print].

PURPOSE: Ventilation and perfusion (VQ) imaging is common following suboptimal CT pulmonary angiogram (CTPA) for pulmonary embolism (PE) evaluation; however, the results of this diagnostic pathway are unclear. The purpose of our study is to determine the incidence of PE diagnosed on VQ scans performed in patients with suboptimal CTPAs.

METHODS: One hundred twenty-two suboptimal CTPAs with subsequent VQ scans within 1 week were retrospectively identified. VQ reports utilizing modified ​prospective investigation of pulmonary embolism diagnosis (PIOPED) and prospective investigative study of acute pulmonary embolism diagnosis (PISAPED) criteria were evaluated for presence of PE; intermediate probability, high probability, and PE present were considered PE positive. Three hundred consecutive reports of each diagnostic CTPA and diagnostic VQ studies were reviewed to estimate baseline PE positive rates at our institution. These were compared to the positive VQ scan rate after suboptimal CTPA by Fisher's exact test. Reported reason for suboptimal CTPA was noted. When contrast bolus timing was suboptimal, we measured main pulmonary artery (mPA) Hounsfield units (HU). Potential alternative diagnoses in CTPA reports were noted.

RESULTS: 97.5% (119/122) of VQ scans following suboptimal CTPA were negative for PE, and 2.5% (3/122) were positive for PE. This was significantly lower than baseline PE positive rate of 10.7% (32/300, p less than 0.01) for VQ imaging, and 10.3% (31/300, p less than 0.01) for CTPA at our institution. Most (79.5%) CTPAs were suboptimal due to contrast timing. Average mPA density in these cases was 164 ± 61 HU. Most of these studies ruled out central PE. Potential alternative diagnosis was reported in 34/122 (28%) of suboptimal CTPAs, for which pneumonia accounted 59%.

CONCLUSION: There is very low incidence of PE diagnosed on VQ imaging performed after suboptimal CTPA. This may be attributed to the ability of most suboptimal CTPAs to rule out central PE.

2. Outcomes for ED Patients With Recent-Onset AF/FL Treated in Canadian Hospitals.

Stiell IG, et al. Ann Emerg Med. 2017 May;69(5):562-571.e2.

STUDY OBJECTIVE: Recent-onset atrial fibrillation and flutter are the most common arrhythmias managed in the emergency department (ED). We evaluate the management and 30-day outcomes for recent-onset atrial fibrillation and flutter patients in Canadian EDs, where cardioversion is commonly practiced.

METHODS: We conducted a prospective cohort study in 6 academic hospital EDs and enrolled patients who had atrial fibrillation and flutter onset within 48 hours. Patients were followed for 30 days by health records review and telephone. Adverse events included death, stroke, acute coronary syndrome, heart failure, subsequent admission, or ED electrocardioversion.

RESULTS: We enrolled 1,091 patients with mean age 63.9 years, atrial fibrillation 84.7%, atrial flutter 15.3%, hospital admission 9.0%, and converted to sinus rhythm 80.1%. Although 10.5% of recent-onset atrial fibrillation and flutter patients had adverse events within 30 days, there were no related deaths and 1 stroke (0.1%). Adjusted odds ratios for factors associated with adverse event were hours from onset (1.03/hour; 95% confidence interval [CI] 1.01 to 1.05), history of stroke or transient ischemic attack (2.09; 95% CI 1.01 to 4.36), and pulmonary congestion on chest radiograph (7.37; 95% CI 2.40 to 22.64). Patients who left the ED in sinus rhythm were much less likely to experience an adverse event (P less than .001).

CONCLUSION: Although most recent-onset atrial fibrillation and flutter patients were treated aggressively in the ED, there were few 30-day serious outcomes. Physicians underprescribed oral anticoagulants. Potential risk factors for adverse events include longer duration from arrhythmia onset, previous stroke or transient ischemic attack, pulmonary congestion on chest radiograph, and not being in sinus rhythm at discharge. An ED strategy of sinus rhythm restoration and discharge in most patients is effective and safe.

3. CPR Research

A. Bystander Efforts Improve 1-Year Outcomes in Out-of-Hospital Cardiac Arrest.

Kragholm K, et al. N Engl J Med. 2017 May 4;376(18):1737-1747.

BACKGROUND: The effect of bystander interventions on long-term functional outcomes among survivors of out-of-hospital cardiac arrest has not been extensively studied.

METHODS: We linked nationwide data on out-of-hospital cardiac arrests in Denmark to functional outcome data and reported the 1-year risks of anoxic brain damage or nursing home admission and of death from any cause among patients who survived to day 30 after an out-of-hospital cardiac arrest. We analyzed risks according to whether bystander cardiopulmonary resuscitation (CPR) or defibrillation was performed and evaluated temporal changes in bystander interventions and outcomes.

RESULTS: Among the 2855 patients who were 30-day survivors of an out-of-hospital cardiac arrest during the period from 2001 through 2012, a total of 10.5% had brain damage or were admitted to a nursing home and 9.7% died during the 1-year follow-up period. During the study period, among the 2084 patients who had cardiac arrests that were not witnessed by emergency medical services (EMS) personnel, the rate of bystander CPR increased from 66.7% to 80.6% (P less than 0.001), the rate of bystander defibrillation increased from 2.1% to 16.8% (P less than 0.001), the rate of brain damage or nursing home admission decreased from 10.0% to 7.6% (P less than 0.001), and all-cause mortality decreased from 18.0% to 7.9% (P=0.002). In adjusted analyses, bystander CPR was associated with a risk of brain damage or nursing home admission that was significantly lower than that associated with no bystander resuscitation (hazard ratio, 0.62; 95% confidence interval [CI], 0.47 to 0.82), as well as a lower risk of death from any cause (hazard ratio, 0.70; 95% CI, 0.50 to 0.99) and a lower risk of the composite end point of brain damage, nursing home admission, or death (hazard ratio, 0.67; 95% CI, 0.53 to 0.84). The risks of these outcomes were even lower among patients who received bystander defibrillation as compared with no bystander resuscitation.

CONCLUSIONS: In our study, we found that bystander CPR and defibrillation were associated with risks of brain damage or nursing home admission and of death from any cause that were significantly lower than those associated with no bystander resuscitation.

B. Practice guideline summary: Reducing brain injury following CPR: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

Geocadin RG, et al. Neurology. 2017 May 10 [Epub ahead of print].

OBJECTIVE: To assess the evidence and make evidence-based recommendations for acute interventions to reduce brain injury in adult patients who are comatose after successful cardiopulmonary resuscitation.

METHODS: Published literature from 1966 to August 29, 2016, was reviewed with evidence-based classification of relevant articles.

RESULTS AND RECOMMENDATIONS: For patients who are comatose in whom the initial cardiac rhythm is either pulseless ventricular tachycardia (VT) or ventricular fibrillation (VF) after out-of-hospital cardiac arrest (OHCA), therapeutic hypothermia (TH; 32-34°C for 24 hours) is highly likely to be effective in improving functional neurologic outcome and survival compared with non-TH and should be offered (Level A). For patients who are comatose in whom the initial cardiac rhythm is either VT/VF or asystole/pulseless electrical activity (PEA) after OHCA, targeted temperature management (36°C for 24 hours, followed by 8 hours of rewarming to 37°C, and temperature maintenance below 37.5°C until 72 hours) is likely as effective as TH and is an acceptable alternative (Level B). For patients who are comatose with an initial rhythm of PEA/asystole, TH possibly improves survival and functional neurologic outcome at discharge vs standard care and may be offered (Level C). Prehospital cooling as an adjunct to TH is highly likely to be ineffective in further improving neurologic outcome and survival and should not be offered (Level A). Other pharmacologic and nonpharmacologic strategies (applied with or without concomitant TH) are also reviewed.

4. Time to Treatment and Mortality during Mandated Emergency Care for Sepsis.

Seymour CW, et al. N Engl J Med. 2017 May 21 [Epub ahead of print].

Background In 2013, New York began requiring hospitals to follow protocols for the early identification and treatment of sepsis. However, there is controversy about whether more rapid treatment of sepsis improves outcomes in patients.

Methods We studied data from patients with sepsis and septic shock that were reported to the New York State Department of Health from April 1, 2014, to June 30, 2016. Patients had a sepsis protocol initiated within 6 hours after arrival in the emergency department and had all items in a 3-hour bundle of care for patients with sepsis (i.e., blood cultures, broad-spectrum antibiotic agents, and lactate measurement) completed within 12 hours. Multilevel models were used to assess the associations between the time until completion of the 3-hour bundle and risk-adjusted mortality. We also examined the times to the administration of antibiotics and to the completion of an initial bolus of intravenous fluid.

Results Among 49,331 patients at 149 hospitals, 40,696 (82.5%) had the 3-hour bundle completed within 3 hours. The median time to completion of the 3-hour bundle was 1.30 hours (interquartile range, 0.65 to 2.35), the median time to the administration of antibiotics was 0.95 hours (interquartile range, 0.35 to 1.95), and the median time to completion of the fluid bolus was 2.56 hours (interquartile range, 1.33 to 4.20). Among patients who had the 3-hour bundle completed within 12 hours, a longer time to the completion of the bundle was associated with higher risk-adjusted in-hospital mortality (odds ratio, 1.04 per hour; 95% confidence interval [CI], 1.02 to 1.05; P less than 0.001), as was a longer time to the administration of antibiotics (odds ratio, 1.04 per hour; 95% CI, 1.03 to 1.06; P less than 0.001) but not a longer time to the completion of a bolus of intravenous fluids (odds ratio, 1.01 per hour; 95% CI, 0.99 to 1.02; P=0.21).

Conclusions More rapid completion of a 3-hour bundle of sepsis care and rapid administration of antibiotics, but not rapid completion of an initial bolus of intravenous fluids, were associated with lower risk-adjusted in-hospital mortality. (Funded by the National Institutes of Health and others.).

5. From the Blogosphere

A. Lit Review: Safety of ondansetron in pregnancy

Mark Mixon, PharmD, Emergency Medicine, May 11, 2017

Nausea and vomiting is a common ailment in pregnancy affecting approximately 70 to 80% of all pregnant women. (1) Ondansetron, a 5-HT3 receptor antagonist, is commonly used to treat nausea and vomiting of varying etiologies including hyperemesis gravidarum. (2) Recently the safety of ondansetron in pregnancy has been called into question. Concern for fetal abnormalities, including cardiac malformations and cleft palates caused by ondansetron have been raised, leading to a petition to the Food and Drug Administration (FDA) to reclassify the agent to category C, D, or X from its current pregnancy category of B. (3) Below we review the pertinent data surrounding the safety of ondansetron in pregnancy…

The largest and most well designed study showed no difference in any major birth defect and no cleft palates in those exposed to ondansetron in the first trimester. (4) Studies suggesting ondansetron may cause cardiac malformations were not well designed, failing to adjust for maternal co-morbidities that could themselves cause cardiac malformations, or were not published in peer reviewed journals, only as abstracts. (5-6) The one study suggesting ondansetron exposure may increase the risk of cleft palates was poorly designed and contained a very small number of patients. (7) The FDA has refused to change the current pregnancy category for ondansetron from a “B” given this evidence.  (3) Based on the current data, ondansetron appears to be a safe agent for the treatment of nausea and vomiting the pregnancy.

When asked about the safety of ondansetron in pregnancy by patients, providers or other emergency department personnel, one can advise that the best available data shows no increase in congenital defects. The benefit of ondansetron use likely outweighs its risk, especially taking into account the adverse fetal effects that maternal electrolyte abnormalities, dehydration, and nutritional deficiency caused by nausea/vomiting may cause. If ondansetron therapy is refused other possible treatment options include pyridoxine, H1-receptor antagonists such as doxylamine, diphenhydramine, and meclizine, or dopamine receptor antagonists such as metoclopramide, promethazine, and prochlorperazine.

B. Resuscitationist’s Guide to Status Epilepticus

Josh Farkas, EMCrit · May 8, 2017

In 2014 I wrote a post suggesting an aggressive, streamlined approach to status epilepticus involving early intubation. The fundamentals of that post remain valid. However, much has changed over the last few years. This post aims to refresh and extend the prior post. It will also serve as a reference to explain my algorithm for status epilepticus in the upcoming Resuscitationist's Crisis Manual.

Overview & philosophy

There are many ways to manage status epilepticus.  Rather than focusing on what may be the theoretically ideal, this post explores an approach which is effective, safe, and feasible.  It's easy to write an algorithm that looks pretty on paper, but harder to create one that works in a crisis.  For example, it's easy to write “administer fosphenytoin after 10 minutes.”  However, the logistics of ordering the drug, receiving it from pharmacy, infusing it at the correct rate, and allowing the body to metabolize it into active phenytoin can take an hour.

The rationale for aggressive treatment of generalized status epilepticus was described previously here.  In short, best outcomes rely upon rapid seizure control.  The longer the seizure continues, the more refractory it becomes to therapy.  The duration of status epilepticus which may cause permanent brain damage is unknown, with experts currently suggesting thirty minutes (Zaccara 2017).  Aside from the brain, persistent status epilepticus may cause aspiration, hyperkalemia, rhabdomyolysis, hyperthermia, myocardial infarction, and arrhythmia…

Speaking of seizure management…

C. Intravenous Versus Nonintravenous Benzodiazepines for the Cessation of Seizures: A Systematic Review and Meta-analysis of RCTs

Alshehri A, et al. Acad Emerg Med. 2017 Mar 25 [Epub ahead of print].

BACKGROUND: The acquisition of intravenous (IV) access in the actively convulsing patient is difficult. This often delays the administration of the IV benzodiazepine (BDZ) necessary for seizure cessation. Delays in seizure cessation are associated with increased pharmacoresistance, increased risk of neuronal injury, worse patient outcomes, and increased morbidity.

OBJECTIVE: The objective was to assess whether the delay imposed by IV access acquisition is justified by improved outcomes. We compared IV versus non-IV BDZ efficacy in the real world with regard to failure rates (primary outcome), interval to seizure control, and observed complications (secondary outcomes).

METHODS: A systematic review was performed using Medline, Embase, and the Cochrane Library. All studies published or in press from the inception of the respective database to July 2016 were included. Only randomized and quasi-randomized controlled trials directly comparing IV to non-IV (buccal, rectal, intranasal, or intramuscular) BDZ were included.

RESULTS: Our search strategy retrieved 2,604 citations for review. A total of 11 studies were finally included in qualitative synthesis and 10 in quantitative analysis. Only one was of high quality. For treatment failure, non-IV BDZ was superior to IV BDZ (odd ratio [OR] = 0.72; 95% confidence interval [CI] = 0.56-0.92). However, no significant difference was found between the two treatments in the pediatric subgroup (OR = 1.16; 95% CI = 0.74-1.81). Non-IV BDZ was administered faster than IV BDZ and therefore controlled seizures faster (mean difference = 3.41 minutes; 95% CI = 1.69-5.13 minutes) despite a longer interval between drug administration and seizure cessation (mean difference = 0.74 minutes; 95% CI = 0.52-0.95 minutes). Respiratory complications requiring intervention were similar between non-IV BDZ and IV BDZ, regardless of administration route (risk difference = 0.00; 95% CI = -0.02 to 0.01).

CONCLUSION: Non-IV BDZ, compared to IV BDZ, terminate seizures faster and have a superior efficacy and side effect profile. Higher-quality studies and further evaluation in different age groups are warranted.

6. Diverticulitis: Can Some Pts Safely Forego Admission? And Antibiotics?

A. Diverticulitis Diagnosed in the Emergency Room: Is It Safe to Discharge Home?

Sirany AE, et al. J Am Coll Surg. 2017 Mar 7 [Epub ahead of print].

BACKGROUND: Inpatient treatment of patients with colon diverticulitis represents a significant financial and clinical burden to the healthcare system and patients. The aim of this study was compare patients with diverticulitis in the emergency department (ED) who were discharged to home versus admitted to the hospital.

STUDY DESIGN: We reviewed all patients evaluated in the ED of a metropolitan health system with the primary diagnosis of diverticulitis (ICD9 562.11) from 2010 through 2012. Only patients diagnosed with computed tomography and those with follow-up were included.

RESULTS: We identified 240 patients; 132 (55%) women, mean age was 59.1 (SD 16.1) years. Imaging findings included extraluminal air (21%), pericolic or pelvic abscess (12%), free fluid (16%), and pneumoperitoneum (6%). 144 (60%) were admitted to the hospital and 96 (40%) were discharged to home on oral antibiotics. Patients admitted to the hospital were more likely to be greater than 65 years (p=0.0007), have a Charlson comorbidity score of over 2 (p=0.0025), to be on steroids or immunosuppressed (p=0.0019), have extraluminal air (p less than 0.0001) or diverticular abscess (p less than 0.0001) on imaging. Median follow-up for all patients was 36.5 months (IQR 25.2- 43). Among patients discharged from the ED, 12.5% returned to the ED or were readmitted within 30 days, with only one patient (1%) requiring emergency surgery, but not until 20 months later. Patients admitted to the hospital had similar rates of readmission (15%; p=0.65).

CONCLUSION: Patients diagnosed with uncomplicated diverticulitis in the emergency room can be safely discharged home on oral antibiotics, as long as CT findings are included in the decision- making process. Patients with complicated diverticulitis on CT scan should be admitted to the hospital with surgical consultation.

Related study: Perhaps antibiotics are also unnecessary?

B. Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis.

Daniels L, et al. Br J Surg. 2017 Jan;104(1):52-61.

BACKGROUND: Antibiotics are advised in most guidelines on acute diverticulitis, despite a lack of evidence to support their routine use. This trial compared the effectiveness of a strategy with or without antibiotics for a first episode of uncomplicated acute diverticulitis.

METHODS: Patients with CT-proven, primary, left-sided, uncomplicated, acute diverticulitis were included at 22 clinical sites in the Netherlands, and assigned randomly to an observational or antibiotic treatment strategy. The primary endpoint was time to recovery during 6 months of follow-up. Main secondary endpoints were readmission rate, complicated, ongoing and recurrent diverticulitis, sigmoid resection and mortality. Intention-to-treat and per-protocol analyses were done.

RESULTS: A total of 528 patients were included. Median time to recovery was 14 (i.q.r. 6-35) days for the observational and 12 (7-30) days for the antibiotic treatment strategy, with a hazard ratio for recovery of 0·91 (lower limit of 1-sided 95 per cent c.i. 0·78; P = 0·151). No significant differences between the observation and antibiotic treatment groups were found for secondary endpoints: complicated diverticulitis (3·8 versus 2·6 per cent respectively; P = 0·377), ongoing diverticulitis (7·3 versus 4·1 per cent; P = 0·183), recurrent diverticulitis (3·4 versus 3·0 per cent; P = 0·494), sigmoid resection (3·8 versus 2·3 per cent; P = 0·323), readmission (17·6 versus 12·0 per cent; P = 0·148), adverse events (48·5 versus 54·5 per cent; P = 0·221) and mortality (1·1 versus 0·4 per cent; P = 0·432). Hospital stay was significantly shorter in the observation group (2 versus 3 days; P = 0·006). Per-protocol analyses were concordant with the intention-to-treat analyses.

CONCLUSION: Observational treatment without antibiotics did not prolong recovery and can be considered appropriate in patients with uncomplicated diverticulitis.

7. Application of the MASCC and CISNE Risk-Stratification Scores to Identify Low-Risk Febrile Neutropenic Pts in the ED

Coyne CJ, et al. Ann Emerg Med. 2017; 69:755–764.

STUDY OBJECTIVE: Although validated risk-stratification tools have been used to send low-risk febrile neutropenic patients home from clinic and inpatient settings, there is a dearth of research evaluating these scores in the emergency department (ED). We compare the predictive accuracy of the Multinational Association for Supportive Care in Cancer (MASCC) and Clinical Index of Stable Febrile Neutropenia (CISNE) scores for patients with chemotherapy-induced febrile neutropenia and presenting to the ED.

METHODS: We conducted a retrospective cohort study to evaluate all patients with febrile neutropenia (temperature ≥38°C [100.4°F], absolute neutrophil count less than 1,000 cells/μL) who presented to 2 academic EDs from June 2012 through January 2015. MASCC and CISNE scores were calculated for all subjects, and each visit was evaluated for several outcome variables, including inpatient length of stay, upgrade in level of care, clinical deterioration, positive blood culture results, and death. Descriptive statistics are reported and continuous variables were analyzed with Wilcoxon rank sum.

RESULTS: During our study period, 230 patients presented with chemotherapy-induced febrile neutropenia. The CISNE score identified 53 (23%) of these patients as low risk and was highly specific in the identification of a low-risk cohort for all outcome variables (98.3% specific, 95% confidence interval [CI] 89.7% to 99.9%; positive predictive value 98.1%, 95% CI 88.6% to 99.9%). Median length of stay was shorter for low-risk versus high-risk CISNE patients (3-day difference; P less than .001). The MASCC score was much less specific (54.2%; 95% CI 40.8% to 67.1%) in the identification of a low-risk cohort.

CONCLUSION: Our results suggest that the CISNE score may be the most appropriate febrile neutropenia risk-stratification tool for use in the ED.

8. On Physician Work Schedules and Payment Models

A. The Effect of Discrete Work Shifts on a Nonterminating Service System

Batt RJ, et al. 2017 Wisconsin University

Hospital emergency departments (EDs) provide around-the-clock medical care and as such are generally modeled as nonterminating queues. However, from the care provider’s point of view, ED care is not a never-ending process, but rather occurs in discrete work shifts and may require passing unfinished work to the next care provider at the end of the shift. We use data from a large, academic medical center ED to show that the patient hazard rate of service completion varies over the course of the shift, and as a result, a patient’s expected treatment time is impacted by when in the doctor’s shift treatment begins. 

We also show that treatment time increases with self-multitasking (the number of patients currently in process with the focal physician), but decreases with co-worker multitasking (the number of patients currently in process with all other physicians). The magnitude of the self-multitasking effect is much larger. Lastly, we show that while treatment time is unaffected by an end-of-shift handoff, patients that have been handed off are more likely to revisit the ED within 3 days, suggesting that patient handoffs lower clinical quality. We use simulation to show that implementing “no new patients” cutoff times can be beneficial in terms of productivity and reduced patient handoffs.

B. Replacing fee-for-service with salary might improve care, reduce burnout

Jeff Lagasse, Associate Editor; Healthcare Finance. May 10, 2017

Economists George Loewenstein and Ian Larkin argue that paying physicians a salary instead of a fee for each service would reduce overuse of tests and procedures. It could also improve their job satisfaction and focus on care.

Economists propose paying physicians salary over fee-for-service method to avoid conflicts of interest Fee-for-service compensation arrangements, they propose, create incentives for physicians to order more services than are best for patients.

In a Journal of the American Medical Association Viewpoint article, a pair of behavioral economists contend that doctors should be paid by salary, rather than the fee-for-service arrangements under which most of them now operate.

While most conflict of interest research and debate in medicine tends to focus on physicians interacting with pharmaceutical and device companies, how doctors are paid is one important source of conflict that's largely ignored in medical literature, they said.

Fee-for-service compensation arrangements, they propose, create incentives for physicians to order more, and different, services than are best for patients.

"Paying doctors to do more leads to over-provision of tests and procedures, which cause harms that go beyond the monetary and time costs of getting them," said George Loewenstein, the Herbert A. Simon University professor of economics and psychology at Carnegie Mellon University, in a statement. "Many if not most tests and procedures cause pain and discomfort, especially when they go wrong."

He and Ian Larkin, an assistant professor of strategy at UCLA's Anderson School of Management, said that a commonly proposed solution to the problem involves requiring physicians to disclose their financial interest for a given procedure. But disclosure of conflicts has been found to have limited, or even negative, effects on patients.

Loewenstein and Larkin argue that the simplest and most effective way to deal with conflicts caused by fee-for-service arrangements is to pay physicians on a straight salary basis. Several health systems well-known for high quality of care, such as the Mayo Clinic, the Cleveland Clinic and the Kaiser group in California, pay physicians salaries without incentives for volume of services performed.

Moving more physicians to straight salary-based compensation might have benefits not only for patients, but also for physicians themselves, they said.

"The high levels of job dissatisfaction reported by many physicians may result, in part, from the need to navigate the complexities of the fee-for-service arrangements," said Larkin. "Instead of focusing on providing patients with the best possible medical care, physicians are forced to consider the ramifications of their decisions for their own paychecks."

9. Controversies in TIA Evaluation and Disposition in the ED

Long B, et al. J Emerg Med. 2017;52(3):299-310.

Background: Transient ischemic attack (TIA) affects over 200,000 patients annually in the United States, and it precedes approximately 14% to 23% of strokes. Patients are typically admitted for evaluation and management.

Objective: This review investigates the controversies of emergency department (ED) evaluation of TIA, including imaging, clinical risk scores, rapid diagnostic protocols, and disposition.

Discussion: TIA is a common condition, with over 200,000 patients affected annually, and is associated with risk of stroke. TIA is defined as a brief episode of neurologic dysfunction with no permanent infarction. A great deal of literature has evaluated the use of imaging, clinical risk scores, and diagnostic protocols in the evaluation of TIA. Head computed tomography noncontrast is not reliable to diagnose acute infarction. Magnetic resonance imaging with diffusion-weighted imaging displays greater diagnostic ability. Carotid imaging includes magnetic resonance angiography, computed tomography angiography, and Doppler with ultrasound. Risk scores that predict future stroke are not reliable when utilized alone. With imaging, including magnetic resonance imaging, patients with low-risk scores can be discharged. The use of ED diagnostic protocols and observation units can reduce length of stay while improving patient treatment and reducing stroke rate. An algorithm is provided for evaluation and disposition in the ED.

Conclusions: TIA is a condition with high risk for stroke. Imaging is often not reliable, nor is the use of risk scores alone. The American College of Emergency Physicians provides a Level B Recommendation for the use of rapid diagnostic protocols to determine patient short-term risk for stroke while avoiding the reliance on stratification instruments to discharge patients from the ED.

Full-text (free with Medscape registration):

10. Images in Clinical Practice

Image diagnosis: Iliopsoas abscess from Crohn disease.

ECG: Male With Chest Pain and Lightheadedness

ECG: Unresponsive Male

Melanoma of the foot

Binaural Tympanic-Membrane Perforations after Blast Injury

Traumatic Spondylolisthesis of the Axis (Hangman’s Fx)

Pyogenic Granuloma of the Conjunctiva

Scarlet Fever

Tuberous Sclerosis Complex

Female With Pain in the Right Shoulder and Chest

Young Infant With Vomiting

Adolescent Female With Headache and Nausea

Woman With Severe Headache

Postural Headache? It’s Not a Tumor!

Earlobe Crease in Patient With Chest Pain

Elderly Male With Neck Stiffness and Fever

Adolescent Female With Abdominal Pain

Man With Painless Oral Lesions

12. Reflections on Physician Experience

A. Letter to a Young Female Physician

Suzanne Koven, M.D. N Engl J Med 2017; 376:1907-1909.

This past June, I participated in an orientation session during which new interns were asked to write self-addressed letters expressing their hopes and anxieties. The sealed envelopes were collected and then returned 6 months later, when I’m sure the interns felt encouraged to see how far they’d come.

This exercise, in which the intern serves as both letter writer and recipient, both novice and veteran, offers a new twist on an old tradition. In 1855, James Jackson published Letters to a Young Physician Just Entering Upon Practice. More recent additions to this epistolary canon include Richard Selzer’s Letters to a Young Doctor, which appeared in 1982, and Treatment Kind and Fair: Letters to a Young Doctor, which Perri Klass published in 2007 on the occasion of her son’s entry into medical school.

When I started my internship 30 years ago, I wasn’t invited to share my hopes and anxieties in a letter — or anywhere else, for that matter. In fact, I recall no orientation at all, other than lining up to receive a stack of ill-fitting white uniforms, a tuberculin skin test, and a hasty and not particularly reassuring review of CPR.

Perhaps the memory of my own abrupt initiation explains my response as I sat at the conference table watching the new interns hunched earnestly over their letters: I was filled with longing. I wanted so much to tell them, particularly the women — more than half the group, I was pleased to note — what I wished I’d known. Even more, I yearned to tell my younger self what I wished I’d known. As the interns wrote, I composed a letter of my own.

Dear Young Female Physician:

I know you are excited and also apprehensive. These feelings are not unwarranted. The hours you will work, the body of knowledge you must master, and the responsibility you will bear for people’s lives and well-being are daunting. I’d be worried if you weren’t at least a little worried.

As a woman, you face an additional set of challenges, but you know that already. On your urology rotation in medical school, you were informed that your presence was pointless since “no self-respecting man would go to a lady urologist.”

There will be more sexism, some infuriating, some merely annoying. As a pregnant resident, I inquired about my hospital’s maternity-leave policy for house officers and was told that it was a great idea and I should draft one. Decades into practice, when I call in a prescription, some pharmacists still ask for the name of the doctor I’m calling for.

And there will be more serious and damaging discrimination as well. It pains me to tell you that in 2017, as I’m nearing the end of my career, female physicians earn on average $20,000 less than our male counterparts (even allowing for factors such as numbers of publications and hours worked)1; are still underrepresented in leadership positions, even in specialties such as OB–GYN in which we are a majority2; and are subjected to sexual harassment ranging from unwelcome “bro” humor in operating rooms and on hospital rounds to abuse so severe it causes some women to leave medicine altogether.3

But there’s also a more insidious obstacle that you’ll have to contend with — one that resides in your own head. In fact, one of the greatest hurdles you confront may be one largely of your own making. At least that has been the case for me. You see, I’ve been haunted at every step of my career by the fear that I am a fraud.

This fear, sometimes called “imposter syndrome,” is not unique to women. Your male colleagues also have many moments of insecurity, when they’re convinced that they alone among their peers are incapable of understanding the coagulation pathway, tying the perfect surgical knot, or detecting a subtle heart murmur.

I believe that women’s fear of fraudulence is similar to men’s, but with an added feature: not only do we tend to perseverate over our inadequacies, we also often denigrate our strengths.

A 2016 study suggested that patients of female physicians have superior outcomes.4 The publication of that finding prompted much speculation about why it might be so: perhaps women are more intuitive, more empathic, more attentive to detail, better listeners, or even kinder? I don’t know whether any of those generalizations are true, but my personal experience and observations make me sure of this: when women do possess these positive traits, we tend to discount their significance and may even consider them liabilities. We assume that anyone can be a good listener, be empathic — that these abilities are nothing special and are the least of what we have to offer our patients.

I have wasted much time and energy in my career looking for reassurance that I was not a fraud and, specifically, that I had more to offer my patients than the qualities they seemed to value most.

Early on, I believed that displaying medical knowledge — the more obscure the better — would make me worthy. That belief was a useful spur to learning, but ultimately provided only superficial comfort. During my second-year clinical skills course, an oncologist asked me to identify a rash. “Mycosis fungoides!” I blurted out, since it was one of the few rashes whose name I knew and the only one associated with cancer. My answer turned out to be correct, causing three jaws to drop at once — the oncologist’s, the patient’s, and my own — but the glow of validation lasted barely the rest of the day.

A little further on in training, I thought that competence meant knowing how to do things…

The rest of the essay (full-text free):

B. Board Review and the Middle-Aged Doctor: What Develops with Life Experience

Anna Reisman, M.D. N Engl J Med 2017; 376:1612-1613

Middle age is the best age to be in this difficult profession, because we are old enough to have suffered ourselves or to have witnessed the suffering of people we love and yet young enough to have the opportunity to pay forward this heightened sensitivity…

Middle age can awaken something like compassion, but it’s more than that. The German word mitgefühl, “with feeling,” marries compassion with condolences, commiseration, and sympathy; the prefix “mit,” or “with,” avows the togetherness, the accompaniment, what the psychiatrist Christine Montross calls abiding with patients. In middle age, that feeling can augment our ability to be there for, to be with our patients, because we may have been there ourselves, or somewhere close enough that we can relate. Imagining the doctor I’d want to have when facing a serious illness, I’d prefer one with a few wrinkles and a greater reserve of lived experience…

13. US-guided interscalene nerve block vs procedural sedation by propofol and fentanyl for anterior shoulder dislocations.

Raeyat Doost E, et al. Am J Emerg Med. 2017 Apr 14 [Epub ahead of print]

BACKGROUND: Few studies were performed to compare ultrasound guided brachial plexus block with procedural sedation for reduction of shoulder dislocations in the Emergency Department (ED). This study was done to provide further evidence regarding this comparison.

METHODS: This was a randomized clinical trial performed on patients presenting with anterior shoulder dislocations to the emergency department of an academic level 2 trauma center. Exclusion criteria were any contraindications to the drugs used, any patient which may not be potentially assigned into both groups because of an underlying medical condition, presence of neurovascular compromise related to the dislocation, presence of concomitant fractures, and patient refusal to participate in the study. Patients were randomly assigned into the Procedural Sedation and Analgesia (PSA) group with propofol and fentanyl or ultrasound guided Inter-Scalene Brachial Plexus Block (ISBPB) with lidocaine and epinephrine.

RESULTS: A total of 60 patients (30 in each group) were included in the study. The emergency room length of stay was significantly lower in the ISBPB group, with mean (SD) values of 108.6 (42.1) vs. 80.2 (25.2) minutes (p=0.005). However, pain scores in the PSA group during reduction showed advantage over ISBPB [0.38 vs. 3.43 (p less than 0.001)]. Moreover, patient satisfaction was higher with PSA (p less than 0.001).

CONCLUSION: Using ISBPB for reduction of anterior shoulder dislocations takes less time to discharge and may make it more feasible in conditions mandating faster discharge of the patient. However, since pain scores may be lower using PSA, this method may be preferred by many physicians in some other situations.

14. Quick Lit Reviews by Ann Emerg Med

A. In Patients With Cardiac Arrest, Does Amiodarone or Lidocaine Increase Meaningful Survival?

Take-Home Message: Among out-of-hospital cardiac arrest patients with shock-refractory ventricular tachycardia or ventricular fibrillation, neither amiodarone nor lidocaine increases survival to hospital discharge or good neurologic outcome.

B. Does Rocuronium Create Better Intubating Conditions Than Succinylcholine for Rapid Sequence Intubation?

Take-Home Message: Succinylcholine is superior to rocuronium in providing excellent intubating conditions for emergency rapid sequence intubation.

C. Comparison of Fresh Frozen Plasma With Prothrombin Complex Concentrate for Warfarin Reversal

Take-Home Message: In patients with intracranial bleeding, prothrombin complex concentrates may have a mortality benefit over fresh frozen plasma for the reversal of warfarin.

D. Should Antiepileptic Drugs Be Initiated in the Emergency Department After a First-Time Seizure?

Take-Home Message: Immediate initiation of antiepileptic drug treatment after an unprovoked first-time seizure may decrease the rate of recurrent seizure, but does not otherwise affect long-term prognosis and is associated with adverse events.

E. Do α2-Adrenergic Agonists Decrease the Symptoms Associated With Opioid Withdrawal?

Take-Home Message: α2-Adrenergic agonists (eg, clonidine) are associated with lower rates of severe withdrawal symptoms and higher rates of adherence; however, this must be balanced with known adverse effects such as hypotension.

15. ED Airway Management of Severe Angioedema: A Video Review of 45 Intubations.

Driver BE, et al. Ann Emerg Med. 2017 May;69(5):635-639.

STUDY OBJECTIVE: Angioedema is an uncommon but important cause of airway obstruction. Emergency airway management of angioedema is difficult. We seek to describe the course and outcomes of emergency airway management for severe angioedema in our institution.

METHODS: We performed a retrospective, observational study of all intubations for angioedema performed in an urban academic emergency department (ED) between November 2007 and June 2015. We performed a structured review of video recordings of each intubation. We identified the methods of airway management, the success of each method, and the outcomes and complications of the effort.

RESULTS: We identified 52 patients with angioedema who were intubated in the ED; 7 were excluded because of missing videos, leaving 45 patients in the analysis. Median time from arrival to the ED to the first intubation attempt was 33 minutes (interquartile range 17 to 79 minutes). Nasotracheal intubation was the most common first method (33/45; 73%), followed by video laryngoscopy (7/45; 16%). Two patients required attempts at more invasive airway procedures (retrograde intubation and cricothyrotomy). The intubating laryngeal mask airway was used as a rescue method 5 times after failure of multiple methods, with successful oxygenation, ventilation, and intubation through the laryngeal mask airway in all 5 patients. All patients were successfully intubated.

CONCLUSION: In this series of ED patients who were intubated because of angioedema, emergency physicians used a range of methods to successfully manage the airway. These observations provide key lessons for the emergency airway management of these critical patients.

16. Epinephrine Concentrations Sufficient in EpiPens Long After the Expiration Date

Cantrell FL, et al. Ann Intern Med. 2017 May 9 [Epub ahead of print]

Background: Interest and outrage have been mounting over dramatic price increases for the emergency-use epinephrine autoinjection device EpiPen (Mylan). Since 2007, the price of this potentially lifesaving medication has risen more than 400%. This sharp increase has caused patients to ask health care practitioners whether they can use expired EpiPens because they cannot afford to replace them.

Objective: To determine whether EpiPens expired up to 50 months retain their stated potency.

Methods: Over 2 weeks, patients and practitioners at a community clinic were asked to provide unused, expired EpiPens. All pens were examined for color changes and expiration date. Two separate aliquots of each EpiPen's content were quantitatively analyzed for epinephrine concentrations by liquid chromatography (Agilent 1260 Infinity II LC, Agilent Technologies)–tandem mass spectrometry (Triple Quad 5500, AB SCIEX). Epinephrine was monitored using 2 transitions (mass–charge ratio, 184.1 to 107.0 and 184.1 to 166.0) and quantified by isotope dilution using epinephrine-d6 as an internal standard.

Results: We collected and analyzed 31 expired EpiPens (epinephrine, 1 mg/mL) and 9 EpiPen Jrs (epinephrine, 0.5 mg/mL) (Table). None was discolored. All were 1 to 50 months past their expiration dates. Nineteen of the EpiPens (65%) and 5 of the EpiPen Jrs (56%) contained at least 90% of their stated amount of epinephrine.

Discussion: Studies have shown that many medications retain full potency up to 40 years beyond their expiration dates (1). However, these studies rarely involve biological agents like epinephrine, which may not maintain their activity as long as other medications. Although medications in the United States are typically assigned expiration dates up to 3 years after manufacture, EpiPens are typically labeled with an expiration date of 18 months or less. One study found that expired EpiPens retained at least 50% of their stated amount of epinephrine up to 90 months past expiration (2), and another found that those less than 25 months past expiration contained at least 90% of the labeled amount (3).

The U.S. Food and Drug Administration permits most medications marketed in the United States to contain 90% to 110% of the labeled concentration of the active ingredients (4). In this study, approximately two thirds of the expired EpiPens and more than half of the expired EpiPen Jrs met this standard and all contained at least of 80% of their labeled concentrations. These findings are important because dosing recommendations for out-of-hospital treatment of anaphylaxis, which are based on anecdotal experience, specify a maximum initial dose of 0.2 to 0.5 mg in adults and 0.01 mg/kg of body weight (with a maximum total dose of 0.3 mg/kg) in children (5). Given that each EpiPen and EpiPen Jr delivers a dose of 3 mL, all of the products tested should deliver a dose within the recommended initial range.
In summary, our data show that EpiPen products can retain substantial amounts of epinephrine well beyond their expiration dates. Although we observed declining concentrations of epinephrine over time, we expect that the dose available 50 months after expiration would still provide a beneficial pharmacologic response. Thus, we conclude that the process for establishing expiration dates for EpiPens should be revised and that, in the setting of outpatient anaphylaxis without other therapeutic alternatives, patients and caregivers should consider the potential benefits of using an expired EpiPen.

17. Efficacy and Safety of Tranexamic Acid in Prehospital Traumatic Hemorrhagic Shock: Outcomes of the Cal-PAT Study

Neeki MM, et al. WJEM 2017 April 19 [Epub ahead of print]

Introduction: The California Prehospital Antifibrinolytic Therapy (Cal-PAT) study seeks to assess the safety and impact on patient mortality of tranexamic acid (TXA) administration in cases of trauma-induced hemorrhagic shock. The current study further aimed to assess the feasibility of prehospital TXA administration by paramedics within the framework of North American emergency medicine standards and protocols.

Methods: This is an ongoing multi-centered, prospective, observational cohort study with a retrospective chart-review comparison. Trauma patients identified in the prehospital setting with signs of hemorrhagic shock by first responders were administered one gram of TXA followed by an optional second one-gram dose upon arrival to the hospital, if the patient still met inclusion criteria. Patients administered TXA make up the prehospital intervention group. Control group patients met the same inclusion criteria as TXA candidates and were matched with the prehospital intervention patients based on mechanism of injury, injury severity score, and age. The primary outcomes were mortality, measured at 24 hours, 48 hours, and 28 days. Secondary outcomes measured included the total blood products transfused and any known adverse events associated with TXA administration.

Results: We included 128 patients in the prehospital intervention group and 125 in the control group. Although not statistically significant, the prehospital intervention group trended toward a lower 24-hourmortality rate (3.9% vs 7.2% for intervention and control, respectively, p=0.25), 48-hour mortality rate (6.3%vs 7.2% for intervention and control, respectively, p=0.76), and 28-day mortality rate (6.3% vs 10.4% for intervention and control, respectively, p=0.23). There was no significant difference observed in known adverse events associated with TXA administration in the prehospital intervention group and control group. A reduction in total blood product usage was observed following the administration of TXA (control: 6.95 units; intervention: 4.09 units; p=0.01).

Conclusion: Preliminary evidence from the Cal-PAT study suggests that TXA administration may be safe in the prehospital setting with no significant change in adverse events observed and an associated decreased use of blood products in cases of trauma-induced hemorrhagic shock. Given the current sample size, a statistically significant decrease in mortality was not observed. Additionally, this study demonstrates that it may be feasible for paramedics to identify and safely administer TXA in the prehospital setting.

18. All NSAIDs Confer Risk of AMI during First Week of Use

by Crystal Phend. Senior Associate Editor, MedPage Today. May 12, 2017

After PRECISION [see below] leveled the playing field for heart risk among nonsteroidal anti-inflammatory drugs (NSAIDs) in a randomized setting, the question of risk with how people really use these painkillers in the real world still wasn't answered.

So researchers did a Bayesian analysis on individual patient data from healthcare database studies to delve into the risk of acute MI specifically in a study reported in BMJ [also below].

Taking any dose of NSAIDs for even one week was associated with an increased risk of MI. As in PRECISION, naproxen didn't earn the cardiovascular safety reputation it has had among NSAIDs. The odds ratios for MI (95% credible intervals) versus no NSAID use in the prior year were:
  • 1.24 (0.91 to 1.82) for celecoxib (Celebrex)
  • 1.48 (1.00 to 2.26) for ibuprofen
  • 1.50 (1.06 to 2.04) for diclofenac
  • 1.53 (1.07 to 2.33) for naproxen
  • 1.58 (1.07 to 2.17) for rofecoxib (Vioxx, withdrawn) 
Higher doses conferred higher risk; but use for longer than one month didn't appear more risky than shorter use.

"Given that the onset of risk of acute myocardial infarction occurred in the first week and appeared greatest in the first month of treatment with higher doses," the group concluded, "prescribers should consider weighing the risks and benefits of NSAIDs before instituting treatment, particularly for higher doses."

A. Risk of AMI with NSAIDs in real world use: bayesian meta-analysis of individual patient data.

Bally M, et al. BMJ. 2017 May 9;357:j1909

Objective To characterise the determinants, time course, and risks of acute myocardial infarction associated with use of oral non-steroidal anti-inflammatory drugs (NSAIDs).

Design Systematic review followed by a one stage bayesian individual patient data meta-analysis.

Data sources Studies from Canadian and European healthcare databases.

Review methods Eligible studies were sourced from computerised drug prescription or medical databases, conducted in the general or an elderly population, documented acute myocardial infarction as specific outcome, studied selective cyclo-oxygenase-2 inhibitors (including rofecoxib) and traditional NSAIDs, compared risk of acute myocardial infarction in NSAID users with non-users, allowed for time dependent analyses, and minimised effects of confounding and misclassification bias. Exposure and outcomes Drug exposure was modelled as an indicator variable incorporating the specific NSAID, its recency, duration of use, and dose. The outcome measures were the summary adjusted odds ratios of first acute myocardial infarction after study entry for each category of NSAID use at index date (date of acute myocardial infarction for cases, matched date for controls) versus non-use in the preceding year and the posterior probability of acute myocardial infarction.

Results A cohort of 446 763 individuals including 61 460 with acute myocardial infarction was acquired. Taking any dose of NSAIDs for one week, one month, or more than a month was associated with an increased risk of myocardial infarction. With use for one to seven days the probability of increased myocardial infarction risk (posterior probability of odds ratio above 1.0) was 92% for celecoxib, 97% for ibuprofen, and 99% for diclofenac, naproxen, and rofecoxib. The corresponding odds ratios (95% credible intervals) were 1.24 (0.91 to 1.82) for celecoxib, 1.48 (1.00 to 2.26) for ibuprofen, 1.50 (1.06 to 2.04) for diclofenac, 1.53 (1.07 to 2.33) for naproxen, and 1.58 (1.07 to 2.17) for rofecoxib. Greater risk of myocardial infarction was documented for higher dose of NSAIDs. With use for longer than one month, risks did not appear to exceed those associated with shorter durations.

Conclusions All NSAIDs, including naproxen, were found to be associated with an increased risk of acute myocardial infarction. Risk of myocardial infarction with celecoxib was comparable to that of traditional NSAIDS and was lower than for rofecoxib. Risk was greatest during the first month of NSAID use and with higher doses.

B. Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis.

Nissen SE, et al. PRECISION Trial Investigators. N Engl J Med. 2016 Dec 29;375(26):2519-29.

BACKGROUND: The cardiovascular safety of celecoxib, as compared with nonselective nonsteroidal antiinflammatory drugs (NSAIDs), remains uncertain.

METHODS: Patients who required NSAIDs for osteoarthritis or rheumatoid arthritis and were at increased cardiovascular risk were randomly assigned to receive celecoxib, ibuprofen, or naproxen. The goal of the trial was to assess the noninferiority of celecoxib with regard to the primary composite outcome of cardiovascular death (including hemorrhagic death), nonfatal myocardial infarction, or nonfatal stroke. Noninferiority required a hazard ratio of 1.12 or lower, as well as an upper 97.5% confidence limit of 1.33 or lower in the intention-to-treat population and of 1.40 or lower in the on-treatment population. Gastrointestinal and renal outcomes were also adjudicated.

RESULTS: A total of 24,081 patients were randomly assigned to the celecoxib group (mean [±SD] daily dose, 209±37 mg), the naproxen group (852±103 mg), or the ibuprofen group (2045±246 mg) for a mean treatment duration of 20.3±16.0 months and a mean follow-up period of 34.1±13.4 months. During the trial, 68.8% of the patients stopped taking the study drug, and 27.4% of the patients discontinued follow-up. In the intention-to-treat analyses, a primary outcome event occurred in 188 patients in the celecoxib group (2.3%), 201 patients in the naproxen group (2.5%), and 218 patients in the ibuprofen group (2.7%) (hazard ratio for celecoxib vs. naproxen, 0.93; 95% confidence interval [CI], 0.76 to 1.13; hazard ratio for celecoxib vs. ibuprofen, 0.85; 95% CI, 0.70 to 1.04; P less than 0.001 for noninferiority in both comparisons). In the on-treatment analysis, a primary outcome event occurred in 134 patients in the celecoxib group (1.7%), 144 patients in the naproxen group (1.8%), and 155 patients in the ibuprofen group (1.9%) (hazard ratio for celecoxib vs. naproxen, 0.90; 95% CI, 0.71 to 1.15; hazard ratio for celecoxib vs. ibuprofen, 0.81; 95% CI, 0.65 to 1.02; P less than 0.001 for noninferiority in both comparisons). The risk of gastrointestinal events was significantly lower with celecoxib than with naproxen (P=0.01) or ibuprofen (P=0.002); the risk of renal events was significantly lower with celecoxib than with ibuprofen (P=0.004) but was not significantly lower with celecoxib than with naproxen (P=0.19).

CONCLUSIONS: At moderate doses, celecoxib was found to be noninferior to ibuprofen or naproxen with regard to cardiovascular safety.

19. US in the ED

A. Diagnostic Value and Effect of Bedside US in Acute Appendicitis in the ED

Gungor F, et al. Acad Emerg Med. 2017 May;24(5):578-586.

OBJECTIVE: Early and accurate diagnosis of acute appendicitis (AA) with ultrasound (US) can minimize the morbidity and mortality of the patients. In this regard, US can help emergency physicians (EPs) in the diagnosing process and clinical decision making for AA. Therefore, we primarily aimed to evaluate the effectiveness of point-of-care US (POCUS) in clinical decision making of EPs for the diagnostic evaluation for AA in the emergency department (ED).

METHODS: The study sample consisted of patients aged greater than 18 years who presented to the ED with abdominal pain and underwent diagnostic evaluation for AA. All patients were examined initially with POCUS by EPs and then with radiology-performed US (RADUS) by radiologists. Pre- and post-POCUS median diagnostic certainty values (MDCVs) for AA were determined with visual analog scale (VAS) scores (0 = not present, 100 = certainly present) by POCUS performers. Definitive diagnoses were determined by surgery, pathologic evaluation of appendectomy specimens, or clinical follow-up results. The sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) for POCUS and RADUS together with pre- and post-POCUS VAS scores for MDCVs were compared.

RESULTS: A total of 264 patients were included into the final analysis and 169 (64%) had a diagnosis of AA. The sensitivity, specificity, PLR, and NLR of US examinations were 92.3% (95% confidence interval [CI] = 87.2%-95.8%), 95.8% (89.5%-98.8%), 21.9 (8.4-57.2), and 0.08 (0.05-0.1) for POCUS and 76.9% (69.8-83%), 97.8% (84.9-99.7%), 36.4 (9.25-144.3), and 0.24 (0.18-0.31) for RADUS, respectively. Pre-POCUS and post-POCUS VAS scores for MDCVs were 60 (interquartile range [IQR] = 50-65) and 95 (IQR = 20-98), respectively (p = 0.000).

CONCLUSION: Point-of-care ultrasonography, when performed in ED for the diagnosis of AA, has high sensitivity and specificity and had a positive impact on the clinical decision making of EPs.

Related article: Magnetic Resonance Imaging Vs US as the Initial Imaging Modality for Pediatric and Young Adult Patients With Suspected Appendicitis

MRI was associated with greater ED LOS and higher costs

B. Point-of-care US for Nonangulated Distal Forearm Fractures in Children: Test Performance Characteristics and Patient-centered Outcomes.

Poonai N, et al. Acad Emerg Med. 2017 May;24(5):607-616.

OBJECTIVES: Distal forearm fractures are the most common fracture type in children. Point-of-care-ultrasound (POCUS) is increasingly being used, and preliminary studies suggest that it offers an accurate approach to diagnosis. However, outcomes such as pain, satisfaction, and procedure duration have not been explored but may be salient to the widespread acceptance of this technology by caregivers and children. Our objectives were to examine the test performance characteristics of POCUS for nonangulated distal forearm injuries in children and compare POCUS to x-ray with respect to pain, caregiver satisfaction, and procedure duration.

METHODS: We conducted a cross-sectional study involving children aged 4-17 years with a suspected nonangulated distal forearm fracture. Participants underwent both x-ray and POCUS assessment. The primary outcome was sensitivity between POCUS and x-ray, the reference standard. Secondary outcomes included self-reported pain using the Faces Pain Scale-Revised, caregiver satisfaction using a five-item Likert scale, and procedure duration.

RESULTS: POCUS was performed in 169 children of whom 76 were diagnosed with a fracture including 61 buckle fractures. Sensitivity of POCUS for distal forearm fractures was 94.7% (95% confidence interval [CI] = 89.7-99.8) and specificity was 93.5% (95% CI = 88.6-98.5). POCUS was associated with a significantly lower median (interquartile range [IQR]) pain score compared to x-ray: 1 (0-2) versus 2 (1-3), respectively (median difference = 0.5; 95% CI = 0.5-1; p less than 0.001) and no significant difference in median (IQR) caregiver satisfaction score: 5 (0) versus 5 (4-5), respectively (median difference = 0, 95% CI = 0, p = 1.0). POCUS was associated with a significantly lower median (IQR) procedure duration versus x-ray: 1.5 (0.8-2.2) minutes versus 27 (15-58) minutes, respectively (median difference = 34.1, 95% CI = 26.8-41.5, p less than 0.001).

CONCLUSIONS: Our findings suggest that POCUS assessment of distal forearm injuries in children is accurate, timely, and associated with low levels of pain and high caregiver satisfaction.

C. ACEP US Guidelines: Emergency, Point-of-Care and Clinical US Guidelines in Medicine

No authors listed. Ann Emerg Med. 2017 May;69(5):e27-e54.

Section 1 – Introduction by Diku P. Mandavia MD, Vivek S. Tayal MD

Ultrasound (US) has become an integral modality in emergency care in the United States during the last two decades. Since the last update of these guidelines in 2008, US use has expanded throughout clinical medicine and established itself as a standard in the clinical evaluation of the emergency patient. There is a wide breadth of recognized emergency US applications offering advanced diagnostic and therapeutic capability benefit to patients across the globe. With its low capital, space, energy, and cost of training requirements, US can be brought to the bedside anywhere a clinician can go, directly or remotely. The use of US in emergency care has contributed to improvement in quality and value, specifically in regards to procedural safety, timeliness of care, diagnostic accuracy, and cost reduction. In a medical world full of technological options, US fulfills the concept of “staged imaging,” where the use of US first can answer important clinical questions accurately without the expense, time, or side effects of advanced imaging or invasive procedures.

Emergency physicians have taken the leadership role for the establishment and education of bedside, clinical, point-of-care US use by clinicians in the United States and around the world. Ultrasonography has spread throughout all levels of medical education, integrated into medical school curricula, through residency, to postgraduate education of physicians, and extended to other providers such as nursing, advanced practice professionals, and prehospital providers. US curricula in undergraduate medical education is growing exponentially due to the leadership and advocacy of emergency physicians. US in emergency medicine (EM) residency training has now been codified in the Accreditation Council for Graduate Medical Education (ACGME) Next Accreditation System (NAS). Emergency US specialists have created the foundation of a subspecialty of ultrasonography that provides the expertise for establishing clinical practice, educating across the educational spectrum, and researching the wide range of applications of ultrasonography. Within healthcare institutions and healthcare systems, emergency physicians are now leading institutional clinical US programs that have used this guideline as a format for multidisciplinary programs.

US imaging and information systems have become more sophisticated and digital over the last decade allowing emergency US examinations to have versatility, mobility and integration. US hardware for emergency care has become more modular, smaller, and powerful, ranging from smartphone size to slim, cart-based systems dedicated to the emergency medicine market. US hardware has evolved to allow on-machine reporting, wireless connectivity and electronic medical record (EMR) and picture archiving and communication system (PACS) integration. A new software entity, US management systems, was created to provide administrative functionality and the integration of US images into electronic records. Emergency physician expertise was integral in the development of these hardware and software advances.

These guidelines reflect the evolution and changes in the evolving world of emergency medicine and the growth of US practice. Themes of universality of practice, educational innovation, core credentialing, quality improvement, and value highlight this new edition of the guidelines. The ultimate mission of providing excellent patient care will be enhanced by emergency physicians and other clinicians being empowered with the use of US.

20. Antibiotic prescription strategies and adverse outcome for uncomplicated lower respiratory tract infections: prospective cough complication cohort (3C) study

Bottom line: Don’t treat “bronchitis” with antibiotics

Little P, et al. BMJ 2017;357:j2148

Objective To assess the impact on adverse outcomes of different antibiotic prescribing strategies for lower respiratory tract infections in people aged 16 years or more.

Design Prospective cohort study.

Setting UK general practice.

Participants 28 883 patients with lower respiratory tract infection; symptoms, signs, and antibiotic prescribing strategies were recorded at the index consultation.

Main outcome measures The main outcomes were reconsultation with symptoms of lower respiratory tract infection in the 30 days after the index consultation, hospital admission, or death. Multivariable analysis controlled for an extensive list of variables related to the propensity to prescribe antibiotics and for clustering by doctor.

Results Of the 28 883 participants, 104 (0.4%) were referred to hospital for radiographic investigation or admission, or both on the day of the index consultation, or were admitted with cancer. Of the remaining 28 779, subsequent hospital admission or death occurred in 26/7332 (0.3%) after no antibiotic prescription, 156/17 628 (0.9%) after prescription for immediate antibiotics, and 14/3819 (0.4%) after a prescription for delayed antibiotics. Multivariable analysis documented no reduction in hospital admission and death after immediate antibiotics (multivariable risk ratio 1.06, 95% confidence interval 0.63 to 1.81, P=0.84) and a non-significant reduction with delayed antibiotics (0.81, 0.41 to 1.64, P=0.61). Reconsultation for new, worsening, or non-resolving symptoms was common (1443/7332 (19.7%), 4455/17 628 (25.3%), and 538/3819 (14.1%), respectively) and was significantly reduced by delayed antibiotics (multivariable risk ratio 0.64, 0.57 to 0.72, P less than 0.001) but not by immediate antibiotics (0.98, 0.90 to 1.07, P=0.66).

Conclusion Prescribing immediate antibiotics may not reduce subsequent hospital admission or death for young people and adults with uncomplicated lower respiratory tract infection, and such events are uncommon. If clinicians are considering antibiotics, a delayed prescription may be preferable since it is associated with a reduced number of reconsultations for worsening illness.

21. Opioid Prescribing

A. Opioid Prescribing by Emergency Physicians and Risk of Long-Term Use

Menchine M, Kea B. N Engl J Med 2017; 376:1895-1896.

To the Editor: Barnett et al. (Feb. 16 issue)1 affirm a key hypothesis: seemingly random clinical exposure to opioids facilitates long-term use, at least among Medicare patients. Without careful inspection, readers may incorrectly interpret this finding to suggest that emergency physicians are key drivers of the opioid epidemic. Nationally, emergency department encounters account for only 5% of all opioids prescribed, even though they constitute more than 10% of all ambulatory visits.2

This study shows that the risk of long-term opioid use after treatment in an emergency department by a “high-intensity prescriber” is small at 1.51%, as compared with a 1.16% risk associated with treatment by a “low-intensity prescriber.” Together these data suggest that interventions in the emergency department to reduce prescribing have a low potential to reduce long-term opioid use. Furthermore, the study is seriously limited, since it does not and cannot compare this effect size against that of providers in other clinical settings where high-dose and long-term opioid prescribing is much more prevalent (e.g., office-based practices that account for greater than 84% of opioid prescriptions).3 Understanding this crucial limitation is key to ensuring that policies do not unjustly focus on opioid prescribing in emergency departments, but rather target the problem of overprescribing of opioids in a comprehensive, multidisciplinary manner.

B. Report shows drop in pain medication prescribing

A QuintilesIMS Institute report showed that in 2016 acetaminophen/hydrocodone dropped to the fourth most prescribed drug in the US, reflecting a 34% decrease in the number of prescriptions since 2012. The report also showed a decrease in prescriptions for all pain medications for the second year a row.

22. Micro Bits

AA. Calling All Clean Freaks! Pay More Attention to Floors, Socks, and Phones

by Angela Ballard, RN, EMT, The Daily Nurse | May 15, 2017

The last time you walked into a patient’s hospital room, what was touching the floor? A purse or briefcase? A cell phone charger? The call button? The TV remote? A blood pressure cuff? Pulse ox? Water bottle?

I don’t know about you, but whenever I see high-touch items like these casually dropped or placed on the hospital floor, I cringe. Until recently, however, I didn’t have any data to back up my revulsion.

For better or for worse, I do now. Yes, bacteria and viruses really can get transferred from patients, to floors, and back up again to other patients, health care providers, and even visitors.
According to a recent study published in the American Journal of Infection Control, patient room floors in five Cleveland-area hospitals were often contaminated with health care-associated pathogens, and objects on the floor frequently resulted in the transfer of pathogens to hands.

Of particular concern, the study found that C. difficile (Clostridium difficile) was the most frequently recovered pathogen from patient room floors. The frequency of contamination was similar in each of the five hospitals studied and in patient rooms and bathrooms, alike.

How should this impact your day-to-day practice? Here’s what I think…

A. Naked mole rats can survive 18 minutes without oxygen. Here’s how they do it

B. AAFP Endorses ACP Guideline on Treating Osteoporosis

May 11, 2017 03:17 pm Chris Crawford – An estimated 54 million adults in the United States have low bone density or osteoporosis. And about half of all Americans older than 50 are at risk for osteoporotic fracture.

In response to this highly prevalent health problem, the American College of Physicians (ACP) has recommended in an evidence-based clinical practice guideline ( that physicians offer pharmacologic therapy with a bisphosphonate -- alendronate (Fosamax), risedronate (Actonel, Atelvia) or zoledronic acid (Reclast) -- or the biologic agent denosumab (Prolia) to reduce the risk for hip and vertebral fractures in women who have known osteoporosis. 

The AAFP has endorsed the guideline, which includes additional recommendations on the appropriate length of pharmacologic therapy in osteoporotic women and against the use of menopausal estrogen therapy to treat the condition. The guideline also recommends against bone density monitoring during treatment and makes specific recommendations for men with clinically recognized osteoporosis and older women with osteopenia.

C. FDA finds no link between fluoroquinolones and retinal, aortic problems

The FDA has issued a drug safety communication update informing the public that its review of patient cases and study findings found no evidence of an association between fluoroquinolone use and retinal detachment or aortic aneurysm and dissection. The agency last year warned that using fluoroquinolones may lead to disabling side effects and that the drugs should only be prescribed when patients have no other treatment options.

D. AIDS treatments add years of life expectancy

The latest antiretroviral medications for AIDS can add 10 years of life expectancy to young patients in the US and Europe, according to a study in The Lancet. Factors include the use of less-toxic drug combinations and better options for individuals with drug-resistant strains of HIV.

E. No arthroscopic surgery for degenerative knee arthritis and meniscal tears: a clinical practice guideline

An expert panel make a strong recommendation against the use of arthroscopy in nearly all patients with degenerative knee disease, based on linked systematic reviews.

F. Weekend effect may be explained by patient-level differences?

Walker AS, et al. Mortality risks associated with emergency admissions during weekends and public holidays: an analysis of electronic health records. Lancet. 2017 May 9 [Epub ahead of print].

BACKGROUND: Weekend hospital admission is associated with increased mortality, but the contributions of varying illness severity and admission time to this weekend effect remain unexplored…

INTERPRETATION: Adjustment for routine test results substantially reduced excess mortality associated with emergency admission at weekends and public holidays. Adjustment for patient-level factors not available in our study might further reduce the residual excess mortality, particularly as this clustered around midday at weekends. Hospital workload was not associated with mortality. Together, these findings suggest that the weekend effect arises from patient-level differences at admission rather than reduced hospital staffing or services.

G. Avoid Processed Red Meat

Etemadi A, et al. Mortality from different causes associated with meat, heme iron, nitrates, and nitrites in the NIH-AARP Diet and Health Study: population based cohort study. BMJ 2017;357:j1957

…Conclusions The results show increased risks of all cause mortality and death due to nine different causes associated with both processed and unprocessed red meat, accounted for, in part, by heme iron and nitrate/nitrite from processed meat. They also show reduced risks associated with substituting white meat, particularly unprocessed white meat.

H. And Eat at Home: Cooking at home positively affects health and finances

This study examined the frequency of home-cooked dinners versus eating out in relation to the Healthy Eating Index (HEI) and food expenditures. Frequent at-home cooking was associated with higher HEI and reduced per capita food expenditures, while frequent eating out was associated with lower HEI and significantly higher per capita food expenditures. Household characteristics associated with frequent home-cooked dinners include being married, being unemployed, having a large household, and having children aged less than 12 years. Education and income were not associated with frequency of home cooking.

I1. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease

In our trial, inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg per deciliter (0.78 mmol per liter) and reduced the risk of cardiovascular events. These findings show that patients with atherosclerotic cardiovascular disease benefit from lowering of LDL cholesterol levels below current targets.

I2. No Effect of Reminder Devices on Medication Adherence: The REMIND Randomized Clinical Trial

J. Implicit Bias in Academic Medicine: #WhatADoctorLooksLike

On October 9, 2016, Tamika Cross posted to Facebook the description of her experience on Delta flight DL945, flying from Detroit to Houston, when she offered to assist with an inflight medical emergency. Dr Cross, an African American woman, is a graduate of Meharry Medical College and is currently a postgraduate year (PGY) 4 physician in obstetrics and gynecology, serving as administrative chief resident at the University of Texas in Houston. Her offers of assistance were first met with patronizing dismissal and subsequently, even when she had persuaded the flight crew that she was a physician, were declined in favor of those of a white man, who offered no evidence that he was a physician. The post went viral #WhatADoctorLooksLike and was followed by a chorus of similar experiences related by other dark-skinned women whose claims that they were physicians were discounted on the basis of their skin color, sex, or both…

K. Same-hospital readmission tied to better HF survival

A study found that Canadian patients with heart failure who were readmitted within 30 days to the same hospital had 11% lower odds of mortality during the hospital stay and tended to be discharged one day sooner than patients admitted to a different hospital than where they originally received care. Researchers stressed the importance of continuity of care for chronic conditions, particularly access to pertinent patient information that may sometimes not be included in discharge summaries.

L. Mortality and early management in elderly acute myocardial infarction patients

One-year mortality of elderly patients with acute myocardial infarction has decreased over the past 15 years. This improvement can be partially credited to the increasing use of recommended management strategies.

M. Study looks at pediatric ED visits for cotton swab-related ear injuries

More than 263,000 US youths younger than 18, or about 34 children daily, were brought to the emergency department due to cotton tip applicator-related ear injuries between 1990 and 2010, and nearly two-thirds of the patients were younger than 8, researchers reported in the Journal of Pediatrics. The findings also showed that foreign body sensation, perforated ear drum and soft tissue injury were the most prevalent injuries.

N. New guidelines update pediatric fruit juice recommendation

Infants younger than age 1 shouldn't be given any fruit juice, while youths ages 1 to 3, 4 to 6 and 7 to 18 should drink no more than 4 ounces, 4 to 6 ounces and 8 ounces of 100% fruit juice daily, respectively, according to an updated American Academy of Pediatrics policy statement in Pediatrics. The recommendations also urged pediatricians to support policies to lower fruit juice consumption and boost whole fruit intake among children.

O. Research links older physicians to higher patient mortality

Hospitalized patients treated by older physicians had a higher 30-day mortality rate, compared with those treated by younger doctors, according to a study in The BMJ. The study also found that the association was not seen among older physicians with high patient volume and that 30-day readmission rates were not affected by physician age.

P. Research analyzes need for routine cholesterol testing

A study in the Annals of Internal Medicine suggests many adults under age 40 may not need routine cholesterol tests. Researchers looked at data on 9,600 adults ages 30 to 49 and found that for nonsmokers with normal blood pressure, there was little heightened risk of a heart attack over the next decade.